CONTROL OF VIRUS INDUCED LYSIS

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Many viruses induce precisely scheduled cell lysis to terminate the infective cycle. The mechanism of this lysis and its temporal regulation will be investigated, initially in the bacteriophages Lambda and PhiX174. The principle lysis proteins, the products of the LambdaS and PhiX174 E genes, will be purified. Antisera raised against these proteins will be used to study the metabolism of these proteins in vivo. The effect of these proteins on the permeability of reconstituted membrane vesicles will be determined. Host mutants resistant to the action of these proteins will be analyzed to determine what structures in the cell are attached by, or resist, the lysis mechanism. Mutations in the viral lysis genes will be analyzed by DNA sequencing to establish functional domains in the lysis protein primary structure. Hybrid fusion genes between S and E will be constructed in vitro, to determine where lysis specificity may be controlled. These methods are expected to resolve the scheduled lysis phenomenon substantially, and to contribute to the general understanding of the membrane transport of proteins. In addition, a self-lysing strain of Escherischia coli will be constructed for use as a cloning vehicle. Finally, the study of lysis mechanisms will be extended to animal viruses. Lysis mutants of influenza virus will be isolated and characterized with the long range goal of developing a therapeutic regimen in which inappropriate lysis is induced in infected cells and thus infection curtailed.